Memory is a complex mental function which includes the ability to learn, retain, and recall information. Memory impairment is often a symptom of dementia, amnesia, aphasia, senility, or age-associated cognitive deterioration. Dementia may be caused by i.a. Alzheimer's disease, Parkinson's disease, progressive supranuclear palsy, and amyotrophic lateral sclerosis.
Two types of memory are generally recognized, viz. short-term and long-term memory. The short-term memory is the ability to learn and briefly retain small amounts of information for a few seconds or minutes and to recall the information again. The long-term memory is the ability to learn and retain large amounts of information and recall those after long delays. Impairment of both types of memory may be symptoms of dementia.
The short-term memory is impaired for persons suffering from dementia in the early stages. Such persons have difficulty in learning new information and to retain it more than momentarily. As the disease progresses, new learning is severely curtailed and, gradually, the long-term memory is also lost.
Several compounds or mixtures of compounds have been suggested in the prior art for the treatment of mental decline.
Pyrrolidone or pyrrolidine derivatives for improving memory have been suggested in EP 239500, EP 165919, BE 892942, U.S. Pat. No. 5,102,882, EP 296978, EP 296979. Pyridine derivatives for the treatment of impairment of short-term memory are disclosed in U.S. Pat. No. 4,448,779. Choline derivatives for treating mental decline in the elderly is suggested in EP 201623. Indole or indolin derivatives for the improvement of processes involved in learning are disclosed in EP 241006, JP 6107544, U.S. Pat No. 5,494,928, WO 97/47598, and U.S. Pat. No. 4,778,812. Pilocardin derivatives for improving memory functions are disclosed in U.S. Pat. No. 4,977,176. Glycine-containing compositions for enhancing cognitive functions are disclosed in U.S. Pat. No. 5,731,349. Peptide derivatives for treating mental decline and improving mental capacity are disclosed in U.S. Pat. No. 5,439,930, RU 2099078, and WO 95/15310. Xanthine derivatives for the treatment of age-related memory impairment are disclosed in WO 94/19349.
Compounds enhancing the stimulus-induced release of neurotransmitters, especially acetylcholine, may also be used to treat memory impairment. Examples are 2-benzyl-2-propyl 2-amino-2-R-acetate derivatives disclosed in EP 293351, 1-(4-chlorophenyl)-2-methyl-2-propyl 2-amino-3-methyl-butanoate disclosed in GB 2205097, polycyclic hetero-aromatic derivatives disclosed in U.S. Pat. No. 5,300,642, 5-phenyl-4,4-dimethyl-3-oxo or hydroxy-pentylamine derivatives disclosed in EP 322391, 1-oxa-8-azaspiro(4.5)decane derivatives disclosed in EP 491562, derivatives of azacyclic and azabicyclic hydroxylamine disclosed in WO 94/00448, halogenated aromatic derivatives disclosed in EP 627400, derivatives of acyclic and cyclic amides disclosed in WO 95/29909, carbamoyloxypropylamine or carbamoyloxyethylamine derivatives disclosed in WO 96/08468.
Compounds that modulate the function of the kainate receptor may be used for improving memory. An example is alkyl carboxy amino acids, such as (2S,4R)-4-methyl glutamic acid, disclosed in WO 96/25387.
In EP 326381 it is suggested to use hypothalamic hypophysiotropic hormones, such as somatostatin and growth-hormone releasing factor, to improve the learning abilities.
DE 2555010 discloses the use of uronic acids for improving the cerebral efficiency in general, such as improvement of memory.
U.S. Pat. No. 4,481,206 discloses the improvement of memory when administering spiro(N′-methyl-4′-piperidyl)-N-ethyl-succinimide. This compound is a parasympathicomimetic substance also having cholinomimetic, analgetic and sedative activity.
WO 98/33498 discloses the use of breflate or analogous compounds thereof for the treatment of a mammal suffering from a cognitive dysfunction. Breflate or analogous compounds thereof enhance the long-term potential of nerve cells.
Phanquinone (4,7-phenanthroline-5,6-dione) has hitherto been used for the treatment of various disorders, such as amoebiasis. However, the treatment or prevention of memory impairment has not been suggested previously. Phanquinone has been marketed by CIBA-GEIGY as ENTOBEX®.
It is the object of the invention to provide a new use of a known pharmaceutical compound for the treatment or prevention of memory impairment. Another object of the invention is to provide a method of treating a subject suffering from or suspected of suffering from memory impairment. A further object of the invention is to provide a method for improving the learning and memory ability of a normal subject.